High-dose-rate interstitial brachytherapy in combination with androgen deprivation therapy for prostate cancer: are high-risk patients good candidates?

BACKGROUND AND PURPOSE: To evaluate the effectiveness of high-dose-rate interstitial brachytherapy (HDR-ISBT) as the only form of radiotherapy for high-risk prostate cancer patients. PATIENTS AND METHODS: Between July 2003 and June 2008, we retrospectively evaluated the outcomes of 48 high-risk patients who had undergone HDR-ISBT at the National Hospital Organization Osaka National Hospital. Risk group classification was according to the criteria described in the National Comprehensive Cancer Network (NCCN) guidelines. Median follow-up was 73 months (range 12-109 months). Neoadjuvant androgen deprivation therapy (ADT) was administered to all 48 patients; 12 patients also received adjuvant ADT. Maximal androgen blockade was performed in 37 patients. Median total treatment duration was 8 months (range 3-45 months). The planned prescribed dose was 54 Gy in 9 fractions over 5 days for the first 13 patients and 49 Gy in 7 fractions over 4 days for 34 patients. Only one patient who was over 80 years old received 38 Gy in 4 fractions over 3 days. The clinical target volume (CTV) was calculated for the prostate gland and the medial side of the seminal vesicles. A 10-mm cranial margin was added to the CTV to create the planning target volume (PTV). RESULTS: The 5-year overall survival and biochemical control rates were 98 and 87 %, respectively. Grade 3 late genitourinary and gastrointestinal complications occurred in 2 patients (4 %) and 1 patient (2 %), respectively; grade 2 late genitourinary and gastrointestinal complications occurred in 5 patients (10 %) and 1 patient (2 %), respectively. CONCLUSION: Even for high-risk patients, HDR-ISBT as the only form of radiotherapy combined with ADT achieved promising biochemical control results, with acceptable late genitourinary and gastrointestinal complication rates.

Objective assessment of dermatitis following post-operative radiotherapy in patients with breast cancer treated with breast-conserving treatment.

PURPOSE: To evaluate radiation dermatitis objectively in patients with breast cancer who had undergone post-operative radiotherapy after breast-conserving surgery. PATIENTS AND METHODS: Skin color (L*, a*, and b* values) and moisture analyses were performed for both breasts (before, after, 1 month, 6 months, and 1 year after radiotherapy) to examine irradiated and non-irradiated skin divided into four quadrants in 118 patients. These patients underwent breast conservative surgery followed by 50 Gy/25 fractions (median) of radiotherapy with or without boost irradiation (10 Gy/5 fractions). RESULTS: L*, a*, and moisture values were changed by irradiation and maximized at completion or 1 month after radiotherapy. One year after radiotherapy, the skin color had returned to the range observed prior to radiotherapy. However, moisture did not return to previous values even 1 year after treatment. The lateral upper side (quadrant C) showed greater changes than other quadrants in the L* value (darker) at the end of radiotherapy. The Common Toxicity Criteria version 3 scores were found to correlate well with a* and L* values at the completion and 1 month after radiotherapy. Boost radiotherapy intensified reddish and darker color changes at the completion of radiotherapy, while chemotherapy did not intensify the skin reaction caused by radiotherapy. CONCLUSION: Moisture impairment as a result of irradiation lasts longer than color alterations. Objective assessments are useful for analyzing radiation dermatitis.

New implant technique for separation of the seminal vesicle and rectal mucosa for high-dose-rate prostate brachytherapy.

PURPOSE: For safer treatment of seminal vesicles (SVs), we initiated a new technique using an anchor applicator for high-dose-rate interstitial brachytherapy (HDR-ISBT) of prostate cancer. METHODS AND MATERIALS: Between January 2004 and March 2005, 23 intermediate- to high-risk patients were treated with HDR-ISBT as monotherapy. Transrectal ultrasonography guided implantation of the treatment applicator in and around the prostate gland and proximal SV. We used an "anchor" applicator to prevent posterior displacement of the SV. After insertion of the anchor applicator, the actual treatment applicator was implanted at the best position for optimal SV coverage. SV coverage was analyzed using a dose-volume histogram. RESULTS: Implantation of the applicator on the posterior side of the SV was successful for 43 of 46 SVs (93%). The median percentage of the SVs receiving the prescribed dose was 41% (range 11-86%). Only one case of acute Grade 2 toxicity (3%) was seen. CONCLUSIONS: Our anchor applicator technique for HDR-ISBT can separate the SV from the rectum. This is the first report of dose-volume histogram analysis of the SV for HDR-ISBT.

New ambulatory implant technique of high-dose-rate interstitial brachytherapy for prostate cancer.

PURPOSE: The aim of this study was to improve the performance status of prostate cancer patients during high-dose-rate interstitial brachytherapy (HDR-ISBT). To this end, we have developed a new ambulatory implant technique. MATERIALS AND METHODS: Ten prostate cancer patients were treated with HDR-ISBT as monotherapy from October 2003 until March 2004. We utilized a new removable template, a flexible applicator with a nonmetallic bead and button stopper, and an inner catheter connecting the applicator and the transfer tube of the brachytherapy unit. We shortened the connector end of the flexible applicator to enable the patient to sit down and walk freely during the treatment time. RESULTS: All 10 patients could walk without any support. No problem in the application was observed. CONCLUSION: Our new ambulatory implant technique for HDR-ISBT was able to improve the performance status of prostate cancer patients.

Preliminary results of MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer.

PURPOSE: To investigate the effectiveness of our novel MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer. METHODS AND MATERIALS: Between June 2005 and June 2009, 29 previously untreated patients with cervical cancer were enrolled (2 T2b, 2 T3a, 19 T3b, and 6 T4 tumors). We implanted MRI-compatible plastic catheters using our unique ambulatory technique. The total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy. RESULTS: The median D90 (high-risk clinical target volume), D(2 cc) (bladder), and D(2 cc) (rectum) per fraction were 6.9, 5, and 4.6 Gy, respectively. The 3-year local control rates were 100%, 95%, and 83% for T2, T3, and T4 tumors, respectively. Grade 3 or 4 late complications occurred in 4 patients. CONCLUSIONS: Our preliminary evaluation of image-based high-dose-rate interstitial brachytherapy showed favorable local treatment results with an acceptable complication rate.

Three-dimensional image-based high-dose-rate interstitial brachytherapy for mobile tongue cancer.

To investigate the influence of a 3D image-based treatment-planning method for high-dose-rate interstitial brachytherapy (HDR-ISBT) for mobile tongue cancer, we analyzed dose-volume histogram results for the clinical target volume (CTV) and the mandible. Between October 2010 and November 2011, one and four patients having T2 and T3 tumors, respectively, were treated with HDR-ISBT. Multiplane implantation using 9-15 treatment applicators was performed. Lugol's iodine staining, metal markers, ultrasonography, and magnetic resonance imaging were used to identify the contours of the gross tumor volume (defined as the CTV). The results of the image-based treatment plan were compared with those of the conventional simulated plan on the basis of a reference point 5 mm from the applicator position. The mean D90(CTV) and V100(CTV) were 112% of the prescribed dose (PD) and 98.1%PD, respectively, for the image-based plan, and 113%PD and 97.2%PD, respectively, for the conventional plan. The median CTVref/Vref was 0.23 for the image-based plan and 0.16 for the conventional plan (P = 0.01). The mean D0.1 cm(3) (mandible), D1 cm(3) (mandible), and D2 cm(3) (mandible) were 80.1%PD, 62.5%PD, and 55.7%PD, respectively, for the image-based plan, and 109.1%PD (P = 0.02), 82.4%PD (P = 0.005), and 74%PD (P = 0.004), respectively, for the conventional plan). Image-based treatment planning may achieve high-conformity radiotherapy for the CTV and decrease irradiated doses to the mandible.

Comparison of dose-volume analysis between standard Manchester plan and magnetic resonance image-based plan of intracavitary brachytherapy for uterine cervical cancer.

To investigate the feasibility of image-based intracavitary brachytherapy (IBICBT) for uterine cervical cancer, we evaluated the dose-volume histograms (DVHs) for the tumor and organs at risk (OARs) and compared results from the IBICBT plan and the standard Manchester system (Manchester plan) in eight patients as a simulation experiment. We performed magnetic resonance imaging (MRI) and computed tomography (CT) following MRI-adapted applicator insertion, then superimposed MR images on the planning CT images to describe the contours of high-risk clinical target volume (HR CTV) and OARs. The median volume of HR CTV was 29 cm(3) (range, 21-61 cm(3)). Median D90 (HR CTV) and V100 (HR CTV) were 116.1% prescribed doses (PD) (90.0-150.8%) and 96.7% (84.2-100%), respectively, for the Manchester plan. In comparison, we confirmed that the median D90 (HR CTV) was 100% PD in the IBICBT plan for all patients. Mean D(2cc) (bladder) was 101.8% PD for the Manchester plan and 83.2% PD for the IBICBT plan. Mean D(2cc) (rectum) was 80.1% PD for the Manchester plan and 64.2% PD for the IBICBT plan. Mean D(2cc) (sigmoid) was 75% PD for the Manchester plan and 57.5% PD for the IBICBT plan. One patient with a large tumor (HR CTV, 61 cm(3)) showed lower D90 (HR CTV) with the Manchester plan than with the IBICBT plan. The Manchester plan may represent overtreatment for small tumors but insufficient dose distribution for larger tumors. The IBICBT plan could reduce OAR dosage while maintaining adequate tumor coverage.

Assessment of daily needle applicator displacement during high-dose-rate interstitial brachytherapy for prostate cancer using daily CT examinations.

To improve treatment conformity for prostate cancer, we investigated daily applicator displacement during high-dose-rate interstitial brachytherapy (HDR-ISBT). Thirty patients treated with HDR-ISBT as monotherapy were examined. All patients received a treatment dosage of 49 Gy per 7 fractions over 4 days. For dose administration, we examined 376 flexible applicators (1128 points) using our unique ambulatory implant technique. Using CT images with a 3-mm slice thickness, we calculated the relative coordinates of the titanium markers and the tips of the applicators. We calculated the distance between the center of gravity of the markers and the tips of the catheters, and compared the distances measured on the day of implantation and the second, third, and fourth treatment days. The mean displacement distance for all applicators was 4.3 ± 3.4 mm, 4.6 ± 4.1 mm, and 5.8 ± 4.5 mm at 21, 45, and 69 hours after initial planning CT. We used a 15-mm margin for needle displacement and only 2 points of 2 patients (16 mm and 18 mm at 69 hours, 2/1128 = 0.2%) exceeded this range. Almost patients (87%) showed the largest displacement within the first 21 hours. The relative doses that covered 100% of CTV (D100(CTV)) values compared with the initial treatment plan were reduced to 0.96 ± 0.08, 0.96 ± 0.08 and 0.94 ± 0.1 at 21, 45 and 69 hours. However, the relative D90(CTV) values kept acceptable levels (1.01 ± 0.02, 1.01 ± 0.03 and 1.01 ± 0.03). Cranial margin of 15 mm seems to be effective to keep D90(CTV) level if we do not do corrective action.

Interstitial brachytherapy using virtual planning and Doppler transrectal ultrasonography guidance for internal iliac lymph node metastasis.

To expand the indications for high-dose-rate interstitial brachytherapy (HDR-ISBT) for deep-seated pelvic tumors, we investigated the usefulness of Doppler transrectal ultrasonography (TRUS) guidance and virtual planning. The patient was a 36-year-old female. She had right internal iliac lymph node oligometastasis of vaginal cancer 12 months after radical radiotherapy. The tumor could not be found by gray-scale TRUS and physical examination. Virtual planning was performed using computed tomography with template and vaginal cylinder insertion. We uploaded the images to our treatment planning software and reconstructed the contours of the clinical target volume (CTV) and right internal iliac vessel. Virtual needle applicators were plotted using the template holes for virtual planning. At the time of implantation, Doppler TRUS was used to prevent vessel injury by needle applicators. Applicators were implanted in accordance with virtual planning and Doppler TRUS could detect the right iliac vessel. The percentage of CTV covered by the prescribed dose was 99.8%. The minimum dose received by the maximally irradiated 0.1-cc volume for the right internal iliac vessel was 95% prescribed dose. Complete response was achieved, however, radiological findings showed marginal recurrence at 15 months after HDR-ISBT. Post-radiation neuropathy occurred as a late complication four months after treatment; however, the pain was well controlled by medication. We consider that virtual planning and Doppler TRUS are effective methods in cases where it is difficult to detect the tumor by physical examination and gray-scale TRUS, thereby expanding the indications for ISBT.

Daily computed tomography measurement of needle applicator displacement during high-dose-rate interstitial brachytherapy for previously untreated uterine cervical cancer.

PURPOSE: We investigated daily needle applicator displacement during high-dose-rate interstitial brachytherapy. METHODS AND MATERIALS: Ten patients with previously untreated uterine cervical cancer received 30Gy in five fractions during 3 days of high-dose-rate interstitial brachytherapy combined with external beam radiotherapy using our unique ambulatory technique. To analyze displacement, we obtained daily computed tomography (CT) images for 147 flexible needle applicators at 21 and 45h after implantation. The distance was defined as the length between the center of gravity of titanium markers and the needle applicator tips along the daily CT axis. We adapted dwell positions of the treatment source to cover clinical target volume with a 15-mm cranial margin. RESULTS: The median displacement was 1mm (range, -6 to 12mm) at 21h and 2mm (range, -9 to 14mm) at 45h, respectively. Statistically significant caudal displacement was observed only between the displacement at 0 and 21h (p<0.0001), and not between the displacement at 21 and 45h (p=0.1). In cases with displacement of 3mm or more, we changed dwell positions to correct the treatment plan. We corrected 45 applicators (31%) at 21h and 67 (46%) at 45h. CONCLUSIONS: We investigated needle applicator displacement in our ambulatory technique using daily CT examination and considered that a 15-mm cranial margin was sufficient to cover clinical target volume.

A dose-volume analysis of magnetic resonance imaging-aided high-dose-rate image-based interstitial brachytherapy for uterine cervical cancer.

PURPOSE: To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). METHODS AND MATERIALS: Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). RESULTS: The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). CONCLUSIONS: Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results.

Needle applicator displacement during high-dose-rate interstitial brachytherapy for prostate cancer.

PURPOSE: To introduce an effective ambulatory technique in high-dose-rate interstitial brachytherapy (HDR-ISBT) for prostate cancer, we investigated the displacement distance using our novel calculation method. METHODS AND MATERIALS: Sixty-four patients treated with HDR-ISBT as monotherapy were examined. Of these, 4, 17, and 43 patients were administered treatment doses of 38 Gy (3 days), 49 Gy (4 days), and 54 Gy (5 days), respectively. For dose administration, we used 776 flexible applicators with a removable template (ambulatory technique). Using CT images, we calculated the relative coordinates of the metal markers and applicators. From these coordinates, to analyze displacement during treatment, we measured the distance between the tip of the needle applicator and the center of gravity of the markers along the average applicator vector. RESULTS: The median displacement distance for all applicators was 7 mm (range, -14 to 24), and that of each treatment schedule was 4, 6, and 9 mm for 38, 49, and 54 Gy, respectively. Of the 776 applicators, displacement of >10 mm was seen in 198 (26%) applicators and >15 mm in 57 (7%) applicators. Body height (p<0.0001) and anticoagulant usage (p<0.0001) were significant factors influencing displacement. CONCLUSIONS: We investigated needle applicator displacement using our unique method. Additional cranial margins are necessary if there is no repositioning of the dwell position. CT scanning should be performed daily during treatment for checking the position of the applicator to detect and rectify the issue of displacement.

Preliminary result of accelerated partial breast irradiation after breast-conserving surgery.

PURPOSE: To investigate the feasibility of accelerated partial breast irradiation (APBI) for Japanese patients, we started high-dose-rate interstitial brachytherapy (HDR-ISBT) as monotherapy after breast-conserving surgery (BCS). METHODS: We implanted 45 Tis-2 breast cancer patients at National Hospital Organization Osaka National Hospital between June 2002 and June 2006. Our eligibility criteria were broader than the ones used previously in western countries. We included margin-positive cases and younger patients (median age: 44; range: 26-68) to adapt the criteria for Japanese women. Total prescribed doses were 36-42 Gy in six to seven fractions, and the volumes encompassed by 100% prescribed dose (V100) were 38.5-315.1 cc. Fifteen patients received chemotherapy. RESULTS: Treatment could be completed for all patients. Two local failures (4%) and two distant metastases were observed, while one patient died of liver metastasis. Seven wound complications, four with and three without infection, and two rib fractures occurred. The significant risk factors for wound complications were non-administration of prophylactic antibiotics during ISBT (P < 0.01), open cavity implant (P < 0.05), large V100 (P < 0.01), V150 (P < 0.05), and V200 (P < 0.05). CONCLUSION: APBI after BCS for Japanese women with relatively small breasts was well tolerated, but special care should be taken with treatment technique.